Journal Article

DZNE-2020-00011

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png A complex of Neuroplastin and Plasma Membrane Ca2+ ATPase controls T cell activation.

Korthals, M. ; Langnaese, K. ; Smalla, K.-H. ; Kähne, T. ; Herrera-Molina, R. ; Handschuh, J. ; Lehmann, A.-C. ; Mamula, D. ; Naumann, M. ; Seidenbecher, C. ; Zuschratter, W. ; Tedford, K. ; Gundelfinger, E.DZNE* ; Montag, D. ; Fischer, K.-D. (Corresponding author) ; Thomas, U.

2017
Macmillan Publishers Limited, part of Springer Nature [London]

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Please use a persistent id in citations: doi:10.1038/s41598-017-08519-4

Abstract: The outcome of T cell activation is determined by mechanisms that balance Ca2+ influx and clearance. Here we report that murine CD4 T cells lacking Neuroplastin (Nptn -/-), an immunoglobulin superfamily protein, display elevated cytosolic Ca2+ and impaired post-stimulation Ca2+ clearance, along with increased nuclear levels of NFAT transcription factor and enhanced T cell receptor-induced cytokine production. On the molecular level, we identified plasma membrane Ca2+ ATPases (PMCAs) as the main interaction partners of Neuroplastin. PMCA levels were reduced by over 70% in Nptn -/- T cells, suggesting an explanation for altered Ca2+ handling. Supporting this, Ca2+ extrusion was impaired while Ca2+ levels in internal stores were increased. T cells heterozygous for PMCA1 mimicked the phenotype of Nptn -/- T cells. Consistent with sustained Ca2+ levels, differentiation of Nptn -/- T helper cells was biased towards the Th1 versus Th2 subset. Our study thus establishes Neuroplastin-PMCA modules as important regulators of T cell activation.

Keyword(s): Animals (MeSH) ; Calcium: metabolism (MeSH) ; Calcium Signaling (MeSH) ; Cell Differentiation (MeSH) ; Cell Membrane: metabolism (MeSH) ; Cell Nucleus (MeSH) ; Gene Expression Regulation (MeSH) ; Lymphocyte Activation (MeSH) ; Membrane Glycoproteins: physiology (MeSH) ; Mice (MeSH) ; Mice, Inbred C57BL (MeSH) ; Mice, Knockout (MeSH) ; Plasma Membrane Calcium-Transporting ATPases: physiology (MeSH) ; T-Lymphocytes: immunology (MeSH) ; T-Lymphocytes: physiology (MeSH) ; Membrane Glycoproteins ; neuroplastin protein, mouse ; Plasma Membrane Calcium-Transporting ATPases ; Atp2b1 protein, mouse ; Calcium

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Contributing Institute(s):

1. U Preclinical Researchers T1 - Magdeburg (U Preclinical Researchers T1 - Magdeburg)

Research Program(s):

1. 341 - Molecular Signaling (POF3-341) (POF3-341)

Appears in the scientific report 2017

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Database coverage:
; ; ; ; BIOSIS Previews ; Clarivate Analytics Master Journal List ; Current Contents - Physical, Chemical and Earth Sciences ; DOAJ Seal ; Ebsco Academic Search ; IF < 5 ; JCR ; SCOPUS ; Web of Science Core Collection ; Zoological Record

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